Blockade Of Persistent Sodium Currents Contributes To The Riluzole-Induced Inhibition Of Spontaneous Activity And Oscillations In Injured Drg Neurons
PLOS ONE(2011)
Abstract
In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I-NaP). The I-NaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I-NaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium-and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I-NaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I-NaP was enhanced in medium-and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I-NaP without affecting the transient sodium current (I-NaT). Taken together, these results demonstrate for the first time that the I-NaP blocker riluzole selectively inhibits I-NaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I-NaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.
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Key words
membrane potential,oscillations,sodium channel,membrane potentials,sodium channels
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